[E244K; E245K] in APOE as reported previously. In addition, he had APOA5 haplotypes associated with hypertriglyceridemia. Laboratory examinations

excluded deficiency of apolipoproteins, lipoprotein lipase, and GPI-HBP1 in this patient. Conclusions: This is, to our knowledge, the first report of severe hypertriglyceridemia and acute pancreatitis in a patient with apo E7. (C) 2014 Elsevier B.V. All rights reserved.”
“A new gas transport model for fractal-like tight porous media is proposed by simultaneously considering the microstructural PCI-32765 order complexity of real porous media, the compressibility of gas, and the gas slippage effect. This model clarifies the gas transport mechanisms in porous media: the total gas flow volume is governed by the weighted addition of viscous flow and slippage flow, and the distribution weighting factor depends on the capillary diameter and the mean free path of the gas. Based on the proposed model, a new permeability model was derived for gas transport in fractal-like tight porous media. The new permeability model does not have any empirical constants, and every parameter in the model has clear physical meaning. The predictions from the model were then

compared with experimental data to show that the model is valid. Furthermore, the parameters influencing gas permeability were analyzed. (C) 2015 AIP Publishing LLC.”
“Our previous studies have demonstrated that the natural chaperone complexes of full-length tumor protein Ags (e. g., gp100)

and large stress proteins (e. g., hsp110 and grp170) with exceptional Ag-holding capabilities augment potent tumor protective immunity. In this study, we assess the peptide-interacting property GDC 0032 cost MLN4924 purchase of these large chaperones and, for the first time, compare the immunogenicity of the recombinant chaperone vaccines targeting two forms of Ags (protein versus peptide). Both hsp110 and grp170 readily formed complexes with antigenic peptides under physiologic conditions, and the peptide association could be further stimulated by heat shock. The large chaperones displayed similar but distinct peptide-binding features compared with hsp70 and grp94/gp96. Immunization with hsp110- or grp170-tyrosinase-related protein 2 (TRP2(175-192)) peptide complexes effectively primed CD8(+) T cells reactive with TRP2-derived, MHC class I-restricted epitope. However, the tumor protective effect elicited by the TRP2(175-192) peptide vaccine was much weaker than that achieved by full-length TRP2 protein Ag chaperoned by grp170. Furthermore, immunization with combined chaperone vaccines directed against two melanoma protein Ags (i.e., gp100 and TRP2) significantly improved overall antitumor efficacy when compared with either of the single Ag vaccine. Lastly, treatment of tumor-bearing mice with these dual Ag-targeted chaperone complexes resulted in an immune activation involving epitope spreading, which was associated with a strong growth inhibition of the established tumors.

Immunohistochemistry showed that TSP-1 was upregulated in both the core of the lesion and in the perilesional area of injured brain tissue. Numerous astrocytes immunopositive for glial fibrillary acidic protein (GFAP) were found in the perilesional Selleckchem C59 wnt area, and TSP-1 was also expressed in almost all astrocytes surrounding blood vessels at 4 days after injury. Next, we examined the influence of vascular basement membrane components on TSP-1 expression. When

astrocytes were cultured on type IV collagen, TSP-1 was significantly upregulated compared with the expression when cells were grown on lamin, fibronectin, or poly-L-lysine. This increase occurred exclusively when astrocytes were grown on the native form of type IV collagen but not on the heat-denatured form or the non-collagenous 1 domain. Further, integrin alpha 1 and beta 1 mRNAs were upregulated concomitantly

with GFAP mRNA, and integrin alpha 1 protein was localized to the endfeet of astrocytes that surrounded blood vessels in the injured brain. Using function-blocking antibodies, we found that the effect of type IV collagen was attributed to integrin alpha 1 beta 1 in primary astrocytes. Collectively, our results suggest that vascular basement membrane components substantially impact gene expression in astrocytes during brain tissue repair. (C) 2010 Wiley-Liss, Inc.”
“The unified method of template preparation for PCR in the form of DNA covered by permeabilized A1155463 cell envelopes was used for the cells of different physiological status (vegetative, dormant forms of different types, and nonviable micromummies). The procedure for the preparation of template DNA included one-stage (boiling in a buffer with chaotropic salts) or two-stage (boiling in a buffer with chaotropic salts followed by treatment with proteinase K) sample preparation. The proposed method proved effective for detection of not only vegetative cells but also of the bacillary spores and the cystlike dormant cells (CLC) of non-spore-forming bacteria. For example, the two-stage sample preparation of Bacillus cereus spores resulted in the PCR sensitivity

increase up to the detection level of 3-30 spores per sample; the one-stage sample preparation was three orders of magnitude less efficient (10(4) spores per sample). An increase in the sensitivity of Stem Cell Compound Library concentration PCR detection (4-10-fold) owing to the use of the two-stage sample preparation was shown for bacillary, staphylococcal, and mycobacterial CLC. The possibility of PCR detection of staphylococcal micromummies with irreversibly lost viability, which were therefore undetectable by plating techniques, was also demonstrated. The application of the unified sample preparation method ensuring efficacious PCR detection of bacterial cells, irrespective of their physiological state, may be a promising approach to more complete detection of microbial diversity and the overall insemination of natural substrates.

Many fluorophores present inside the living cells such as NADH + H(+), tryptophan, pyridoxine, and riboflavin fluoresce at specific excitation and emission wavelength combinations. Since these key intracellular metabolites are involved in cell

growth and metabolism, their concentration change at any time inside the cell could reflect the changes in cell metabolic activity. NADH + H(+) spectrofluorometry was used for on-line characterization of physiological state during batch cultivation of poly-beta-hydroxybutyric acid (PHB) production by Wautersia eutropha. The culture fluorescence increased with an increase in the biomass concentration with time. A linear correlation between cell mass concentration and net NADH + H(+) fluorescence was established during active growth phase (13 to 38 h) of batch CT99021 concentration cultivation. The rate of CCI-779 manufacturer change of culture fluorescence (dF/dt) exhibited a gradual increase during the predominantly growth phase of batch cultivation (till 20 h).

Thereafter, a sudden drop in the dF/dt rate and its leveling was recorded indicating major changes in culture metabolism status which synchronized with the start-up of accumulation of PHB. After 48 h, yet another decrease in the rate of change of fluorescence (dF/dt) was observed primarily due to severe substrate limitation in the reactor. On-line NADH + H(+) fluorescence signal and its rate (dF/dt) could therefore be used to distinguish the growth, product formation, and nutrient depletion stage (the metabolic state marker) during the batch

cultivation of W. eutropha.”
“Systemic RNAi in Caenorhabditis elegans requires the widely conserved transmembrane protein SID-1 to transport RNAi silencing signals between cells. When expressed in Drosophila S2 cells, C. elegans SID-1 enables passive dsRNA uptake from the culture medium, suggesting that SID-1 functions as a channel for the transport of double-stranded RNA (dsRNA). Here we show that nucleic acid transport by SID-1 is specific for dsRNA and that addition of dsRNA to SID-1 ACY-241 mouse expressing cells results in changes in membrane conductance, which indicate that SID-1 is a dsRNA gated channel protein. Consistent with passive bidirectional transport, we find that the RNA induced silencing complex (RISC) is required to prevent the export of imported dsRNA and that retention of dsRNA by RISC does not seem to involve processing of retained dsRNA into siRNAs. Finally, we show that mimics of natural molecules that contain both single-and double-stranded dsRNA, such as hairpin RNA and pre-microRNA, can be transported by SID-1. These findings provide insight into the nature of potential endogenous RNA signaling molecules in animals.”
“Purpose Therapeutic hypothermia has become the standard treatment for unconscious patients in cardiac arrest.

\n\nDesign:\n\nProspective, observational study.\n\nSetting:\n\nSingle center.\n\nPatients:\n\nWe enrolled 336 consecutive children (median age, 6 mo [range, 0-37 mo]) undergoing cardiac surgery (87 neonates; age, 7 d [5-12]; median, 25th-75th percentile; 24 infants and children; age, 11 mo [4-60]) and 436 healthy controls.\n\nInterventions:\n\nBrain natriuretic peptide was measured selleck products preoperatively, on every postoperative day in the ICU, and at discharge. Intubation time was the primary outcome.\n\nMeasurements and Main

Results:\n\nPreoperative brain natriuretic peptide values in patients with congenital heart disease were higher than those in controls (p < 0.01). Brain natriuretic peptide had a good diagnostic accuracy in discriminating between patients with congenital

heart disease and healthy controls with an area under the curve = click here 0.918 for neonates and area under the curve = 0.894 for older children. The best cutoff values, calculated by receiver operating characteristic analysis, were different for the two age subgroups with cutoff values of 363.5 ng/L for neonates and 23.5 ng/L for older children. At 24 hours after surgery, although brain natriuretic peptide decreased in neonates (baseline 2723 vs 1290 ng/L, p < 0.001), it increased in children (60 vs 365 ng/L at 24 hours, p < 0.001). Multivariable analysis identified the preoperative level of brain natriuretic peptide in infant/children and the difference in GSK923295 inhibitor brain natriuretic peptide value (baseline 24 hours) in neonates, as independent predictors of intubation time. Furthermore, body surface area, Aristotle score, and cardiopulmonary bypass time had an

independent significant effect on the endpoint in either group.\n\nConclusions:\n\nBaseline cardiac endocrine function and its response to surgical stress are dependent on age in neonates and children, undergoing cardiac surgery for congenital heart disease. Brain natriuretic peptide shows a good diagnostic and prognostic accuracy in this setting, with different features in either neonates or infants/children subsets.”
“Dengue virus is the flavivirus that causes dengue fever, dengue hemorrhagic disease, and dengue shock syndrome, which are currently increasing in incidence worldwide. Dengue virus protease (NS2B-NS3pro) is essential for dengue virus infection and is thus a target of therapeutic interest. To date, attention has focused on developing active-site inhibitors of NS2B-NS3pro. The flat and charged nature of the NS2B-NS3pro active site may contribute to difficulties in developing inhibitors and suggests that a strategy of identifying allosteric sites may be useful. We report an approach that allowed us to scan the NS2B-NS3pro surface by cysteine mutagenesis and use cysteine reactive probes to identify regions of the protein that are susceptible to allosteric inhibition.

\n\ncenter dot Given that family history can be easily assessed in routine clinical practice, it should be regarded as an important parameter to consider alongside PSA level for prostate cancer risk assessment.”
“Enterotoxigenic Escherichia coli (ETEC) are the most common bacterial pathogens causing diarrhea in developing countries where they lead to hundreds of thousands of deaths, mostly in children. These organisms are a leading cause of diarrheal illness in travelers to endemic countries. ETEC pathogenesis, and consequently vaccine approaches, have largely focused on plasmid-encoded enterotoxins or fimbrial colonization factors. To date

these approaches have not yielded a broadly protective vaccine. However, recent studies suggest that ETEC pathogenesis is more complex than previously appreciated and involves additional AZD6244 nmr plasmid and chromosomally encoded virulence molecules β-Nicotinamide mw that can be targeted in vaccines. Here, we review recent novel antigen discovery efforts, potential contribution of these proteins to the molecular pathogenesis of ETEC and protective immunity, and the potential implications for development of next generation vaccines for important pathogens. These proteins may help to improve the effectiveness of future vaccines by making them simpler and possibly broadly protective because of their conserved nature.”
“The purpose of this study was to investigate

bovine bile induced protein changes within Trichinella spiralis muscle larvae (ML) in vitro. The larvae were activated by 5% raw bovine bile diluted in saline and in serum-free RPMI-1640 medium at 37 degrees C in 5% CO2 for 2 h and, respectively. The crude and excretory secretory (ES) antigens

from NIL were analyzed by SDS-PAGE and Western Nutlin-3a molecular weight blot. Following activation and comparison to blots of non-activated ML, blots of activated T. spiralis crude worm extract gave rise to three new protein bands (133, 125, and 26 kDa) when screened with mouse infection sera, and four new bands (125, 116, 80, and 29 kDa) when screened with sera from mice immunized with ES antigen. In the same screenings, a loss of two bands migrating at 106 and 25 kDa, and three bands migrating at 76, 58, and 16 kDa, respectively, was observed. When ES antigens from activated ML were blotted and compared to non-activated ML, four new bands (136, 39, 38, and 36 kDa) and seven new bands (136, 120, 100, 39, 36, 34, and 31 kDa) appeared when screened with infection sera and ES immune sera, respectively. In the same comparison, two bands migrating at 67 and 20 kDa, and ten bands migrating at 132,112, 33, 32, 26, 23, 21,19,16, and 15 kDa, were no longer recognized by the ML infection sera and immune sera, respectively. The results showed that after the ML were activated by bile, their protein profiles changed.

Due to these efforts and the costs of the analyses, serial sampling is feasible in an experimental setting, but not for measurements on a routine basis. The present study focuses on the feasibility of an innovative, noninvasive spectroscopic technique that allows in vivo measurements of carotenoids in the skin by reflection spectroscopy. To this end, in a first trial, repeated measurements of the carotenoid

concentration of the udder skin were performed on 25 healthy cattle from different breeds. Carotenoid concentrations showed Ispinesib in vivo highly significant differences between individual animals (P < 0.001), although they were kept under the same environmental conditions and received the same diet. The carotenoid concentrations in “sensitive” and “robust” cows (evaluated by a temperament test) differed significantly (P < 0.005), with higher concentrations observed in robust cows. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.10.101514]“
“Background: The only published US study,

on racial/ethnic disparities in inpatient asthma management was performed in 1989-1990 at a single center. The authors reported that black and Hispanic children were provided substandard care at hospital discharge compared to white children. The purpose of the present analysis was to reexamine this important issue in a large multicenter study.\n\nMethods: Wnt assay A cohort study of 1,232 children and adults hospitalized with a physician diagnosis of acute asthma at 30 hospitals in 22 US states was used.\n\nResults: The cohort included 562 children (age range, 2 to 17 years; 39% white; 42% black; and 19% Hispanic) and 670 adults (age range, 18 to 54 years; 44% white; 44% black; and 12% Hispanic). There were no significant

racial/ethnic differences in the choice of inpatient medications or length of stay among either children or adults. At hospital discharge, Hispanic children were less likely to receive an asthma action plan (37%) compared to white children (60%) or black children (63%; p < 0.001). Multivariate adjustment for eight variables (including socioeconomic status, hospital admissions for asthma in the past year, medication use prior to presentation, physical examination findings, selleck chemical and hospital admission location) attenuated the statistical significance of this association (odds ratio, 0.5; 95% confidence interval, 0.1 to 2.5).\n\nConclusions: We did not identify racial/ethnic disparities in the inpatient treatment and outcomes for children or adults with acute asthma. At hospital discharge, Hispanic children were less likely to receive an asthma action plan compared to white or black children, possibly due to language or socioeconomic differences. (CHEST 2009; 135:1527-1534)”
“Background: Pooling is a cost effective way to collect data for genetic association studies, particularly for rare genetic variants.

Conclusions: PIVKA-II is useful for determining patient survival and the risk of recurrence in modified UICC T3 stage HCC patients.”
“Background. There is evidence to support that nutritional deficiency can reduce the body’s immune function,

thereby decreasing resistance to Fedratinib mouse disease and increasing susceptibility to intestinal parasites. Methods. A cross-sectional survey was carried out on 693 school-aged children from 5 schistosomiasis-endemic villages in Northern Samar, the Philippines. Data on dietary intake, nutritional status, and intestinal parasitic infection were collected. Results. The prevalence of stunting, thinness, and wasting was 49.2%, 27.8%, and 59.7% of all children. The proportion of children infected with Schistosoma japonicum (15.6%, P = .03) and

SB203580 hookworm (22.0%, P = .05) were significantly lower among children who met the recommended energy and nutrient intake (RENI) for total calories. The percentage of children infected with Trichuris trichiura was highest among children who did not meet the RENI for energy (74.1%, P = .04), iron (73.4%, P = .01), thiamine (74.0%, P = .00), and riboflavin (73.3%, P = .01). Susceptibility to having 1 or more parasitic infections was significantly associated with poor intake of energy (P = .04), thiamine (P = .02), and riboflavin (P = .01). The proportion of stunted children was significantly higher among children who did not meet the RENI for energy (68.9%, P = .002), protein (54.0%, P = .004), or niacin (30.8%, P = .02) and for those infected with hookworm (31.8%, P = .0002). After adjusting for potential confounders, protein intake less than the RENI (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.03-2.14), and hookworm infection (OR, 1.77; 95% CI, 1.22-2.55) were the major predictors of stunting. Conclusions. The results support the hypothesis that poor nutrient intake may increase susceptibility to parasitic diseases and together Baf-A1 supplier they negatively affect childhood nutritional

status.”
“The regulation of mammalian myocardial carbohydrate metabolism is complex; many factors such as arterial substrate and hormone levels, coronary flow, inotropic state and the nutritional status of the tissue play a role in regulating mammalian myocardial carbohydrate metabolism. The Pyruvate Dehydrogenase Complex (PDHc), a mitochondrial matrix multienzyme complex, plays an important role in energy homeostasis in the heart by providing the link between glycolysis and the tricarboxylic acid (TCA) cycle. In TCA cycle, PDHc catalyzes the conversion of pyruvate into acetyl-CoA. This review determines that there is altered cardiac glucose in various pathophysiological states consequently causing PDC to be altered.

The phenol-sulfuric acid method Pfizer Licensed Compound Library was used to quantify polysaccharides, and the monosaccharide composition of the polysaccharides was determined by gas chromatography. Stepwise discriminant analysis was used to differentiate among the five closely related species based on the chemical composition analysis. This proved to be a simple and accurate approach for discriminating among these species. The results also showed that the polysaccharide content, the amounts of the four low molecular weight compounds, and the mannose to glucose ratio,

were important factors for species discriminant. Therefore, we propose that a chemical analysis based on quantification of naringenin, bibenzyl, and polysaccharides is effective for identifying D. officinale.”
“Objective. The authors performed phase I/II clinical trial to evaluate the toxicity and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced squamous cell carcinoma of the uterine cervix.\n\nMethods. Between April 2000 and January 2006, 22 patients for Protocol 9902 were treated with C-ion RT.

The number of patients with stage IIB, VX-770 solubility dmso IIIB, and IVA diseases was 1, 18, and 3, respectively. All patients had bulky tumors measuring 4.0-12.0 cm (median 6.2 cm). The whole pelvic dose was fixed at 39.0 GyE for 13 fractions, and additional 15.0 GyE for 5 fractions was given to the gross tumor volume (GTV) and surrounding tissues.

With regard to local boost, a dose-escalation study was planned for 2 fractions to GTV. Total see more dose to the cervical tumor was 64.0-72.0 GyE for 20 fractions.\n\nResults. All patients completed the scheduled therapy and no patient developed Grade 2 or higher acute toxicity. There was no Grade 3 or higher late complications at each dose. The 5-year overall survival rate and local control rate were 50.0% and 68.2%, respectively. Seven out of the 16 patients who received 64.0-68.0 GyE developed local recurrences, but all patients who received 72.0 GyE maintained local control.\n\nConclusions. There were no severe acute or late complications in this trial. C-ion RT has the potential to improve the treatment for locally advanced bulky cervical cancer by applying a total dose of 72.0 GyE, with the results lending incentive to further investigations to confirm the therapeutic efficacy. (C) 2013 Elsevier Inc. All rights reserved.”
“We studied the dose-dependent cardiotoxic effect of propranolol. Intraperitoneal injection of propranolol in doses of 1 and 2 mg/100 g body weight produced a potent effect on central hemodynamics and myocardial contractility, impaired diastolic relaxation, and caused damage to cardiomyocyte membranes due to activation of free radical oxidation.

To better define the physiological properties of NG2(+) cells, we used transgenic mice that allowed an unbiased sampling of this population and unambiguous identification of cells in discrete states of differentiation. Using acute brain slices prepared from developing and mature mice, we found that NG2(+) cells in diverse brain regions share a core set of physiological properties, including expression of voltage-gated Na(+) (NaV) channels and ionotropic glutamate receptors, and formation of synapses with glutamatergic neurons. Although small amplitude Na(+) spikes could be elicited in some NG2(+) cells during the first postnatal week, they were not capable of generating action potentials. Transition of these

progenitors to the premyelinating stage was accompanied by VX-770 research buy LY2606368 the rapid removal of synaptic input, as well as downregulation of AMPA and NMDA receptors and NaV channels. Thus, prior reports of physiological heterogeneity among NG2(+) cells may reflect analysis of cells in later stages of maturation. These results suggest that NG2(+) cells are uniquely positioned within the oligodendrocyte lineage to monitor the firing patterns of surrounding neurons.”
“Cellulase was immobilized on chitosan by the method of covalent binding. The optimum immobilized conditions were as follow: the pH value was 5.0, the glutaraldehyde concentration was 0.015 (w/v) and the formaldehyde concentration was 0.15 (w/v). Both the free

and immobilized cellulase were characterized by determining the pH, temperature, thermal stability and storage stability. The optimum pH of both the free and immobilized cellulase was found as 4. The immobilized cellulase had optimum temperature of 50 degrees C as compared to 40 degrees C in case of free enzyme. The immobilized enzyme showed higher thermal stability than the free cellulase, after 120 min, the this website activity of immobilized cellulose and the free enzyme retained 86.5 and 61%

respectively. After 11 cycles, the activity of the immobilize enzyme conserved 80.27%. The immobilized enzyme exhibited slightly better storage stability than the free enzyme. The Km and Vm values for the immobilized and free cellulase were 8.1 and 1.84 mg/L and 0.01 and 0.0036 mg/ml/min respectively. Cellulose hydrolysis by immobilized cellulase in the presence of a 88 ionic liquid (IL), 1,3-dimethylimidazolium dimethylphosphate (MMIM-DMP), was investgated. The result showed that the addition of 20% (v/v) MMIM-DMP gave the highest initial rate, which was 1.3 and 13.9 times higher than the hydrolysis rate in citric acid – sodium hydrogen phosphate buffer and in IL, respectively.”
“Animals are known to exhibit ‘personality’; that is, individual differences in behaviour that are consistent across time and/or situations. One axis of personality of particular importance for behavioural ecology is boldness, which can be defined as the tendency of an individual to take risks.

(Fertil Steril(R) 2010;94:574-80. (C) 2010 by American Society for Reproductive Medicine.)”
“Here we have developed protocols using the baboon as a complementary alternative Old World Primate to rhesus and other macaques which have severe limitations in their availability. Baboons are not limited

as research resources, they are evolutionarily closer to humans, and the multiple generations of pedigreed colonies which display complex human disease phenotypes all support their further optimization as an invaluable primate model. Since neither baboon-assisted reproductive technologies nor baboon embryonic stem cells (ESCs) have been reported, here we describe the first derivations and characterization of baboon ESC lines from IVF-generated blastocysts. Two ESCs lines (BabESC-4 and BabESC-15) SN-38 research buy display ESC morphology, express pluripotency markers (Oct-4, hTert, Nanog, Sox-2, Rex-1, TRA1-60, Alvespimycin chemical structure TRA1-81), and maintain stable euploid female karyotypes with parentage confirmed independently. They have been grown continuously for >430 and

290 days, respectively. Teratomas from both lines have all three germ layers. Availabilities of these BabESCs represent another important resource for stem cell biologists. (C) 2009 Elsevier B.V. All rights reserved.”
“Our study is to investigate whether tyrosine kinase receptor B (TrkB) is expressed in eutopic endometrium of women with adenomyosis and its association with clinical characteristics.\n\nWe collected endometrial tissues from 31 women with adenomyosis and 30 adenomyosis-free women undergoing surgery for benign indications. TrkB expression was assessed by immunohistochemistry and reverse-transcription polymerase chain reaction.\n\nImmunoreactive staining for TrkB was present as brown flocculent precipitate in the endometrial cells. The average level of TrkB protein (quantitation STI571 mw of immunostaining intensity) in secretory endometrial samples of women with adenomyosis was significantly higher than that in controls (p < 0.01). The average level of TrkB messenger RNA (mRNA) expression of women with adenomyosis was significantly

higher than that of controls at secretory phase (p < 0.01). In addition, the immunostaining quantitation of TrkB protein was positively correlated with the serum CA125 (r = 0.308, p = 0.016) and dysmenorrhea (r = 0.393, p = 0.002).\n\nOur study revealed elevation of TrkB protein and mRNA expression in the secretory endometrium of women with adenomyosis. Moreover, TrkB protein expression in human endometrium was positively correlated with the serum CA125 and dysmenorrhea. TrkB might contribute to the pathogenesis and progression of adenomyosis.”
“Ubiquinone-10 (CoQ10), a vitamin-like lipophilic component of the membrane-bound electron transport system, has a wide range of therapeutic, neutraceutical, and cosmeceutical applications.